1.Effect of Huanglian Jiedutang in Regulating Ferroptosis in Mice with Atherosclerosis Based on Nrf2/GPX4 Signaling Pathway
Zhaohui GONG ; Li GAO ; Huiqi ZHAI ; Jinzi YU ; Qingmin CHU ; Chuanjin LUO ; Lijin QING ; Wei WU ; Rong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):22-28
ObjectiveTo study the mechanism of Huanglian Jiedutang (HLJDT) in treating mice with atherosclerosis (AS) by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group, and 50 ApoE-/- mice were randomly divided into five groups: model group, low-dose group of HLJDT, medium-dose group of HLJDT, high-dose group of HLJDT, and atorvastatin (ATV) group. ApoE-/- mice were fed a high-fat diet for eight weeks to establish the AS model, and at the 9th week, they were given normal saline, low, medium, and high doses of HLJDT (3.9, 7.8, 15.6 g·kg-1·d-1), and atorvastatin calcium tablets (0.01 g·kg-1·d-1), respectively, for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) in blood fat were measured by the automatic biochemical analyzer, and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase (SOD) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The content of reduced glutathione (GSH) in serum was detected by the microplate method, and that of malondialdehyde (MDA) in serum was detected by the TBA method. The protein expression of nuclear factor E2-associated factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway was detected by Western blot. ResultsCompared with those of the normal group, the contents of TC, LDL-C, TG, HDL-C, and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased (P<0.01), while the expression levels of SOD and GSH in serum, as well as Nrf2, solute carrier family 7 member 11 (SLC7A11), and GPX4 in aorta were significantly decreased (P<0.01). Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta, volume atrophy, mitochondrial crista reduction, or a loose and disorganized form. Compared with those in the model group, the aortic vascular plaque deposition was significantly decreased in the low-dose, medium-dose, and high-dose groups of HLJDT and ATV group, and the contents of serum TC, LDL-C, TG, and MDA in serum were significantly decreased (P<0.05, P<0.01). The contents of serum SOD and GSH and the expression levels of Nrf2, SLC7A11, and GPX4 in the aorta were increased (P<0.05, P<0.01), and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased, and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition, decrease blood lipid and MDA expression, increase SOD and GSH expression, and ameliorate the pathological changes of ferroptosis, the mechanism of which is related to the Nrf2/GPX4 signaling pathway.
2.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
3.Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis
Zonglong LI ; Jialu CHEN ; Yue TANG ; Delong QIN ; Chen CHEN ; Yinghe QIU ; Hong WU ; Yu HE ; Xianhai MAO ; Wenlong ZHAI ; Jingdong LI ; Xiao LIANG ; Chuandong SUN ; Kai MA ; Zhimin GENG ; Zhaohui TANG ; Zhiwei QUAN
Chinese Journal of Surgery 2024;62(7):685-696
Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.
4.Clinical effect of stromal vascular fraction gel injection on local rhinoplasty
Dongyue LI ; Zhaohui ZHAI ; Tao CHEN ; Chun'an QU ; Xin ZHANG ; Shengjian TANG
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(2):104-108
Objective:To observe the application and clinical effect of stromal vascular fraction gel (SVF-gel) in local rhinoplasty.Methods:A total of 84 patients with mild nasal root and low bridge were divided into observation group and control group. In the observation group, liposuction with SVF gel extraction plus injection rhinoplasty was carried out; in the control group, liposuction plus injection rhinoplasty was carried out according to the height change of nasal root and bridge, the change of nasal frontal angle, the occurrence of complications and the satisfaction of patients after operation.Results:The 84 patients were followed up for 2 weeks to 24 months. The height of nasal root and bridge increased significantly and the lines were more harmonious. The absorption of the observation group was much lower than that of control group. Except 3 patients in the observation group and 8 patients in the control group, there were different degrees of absorption within 6 months after operation. All patients did not have complications such as fat liquefaction, necrosis, induration and infection in the injection area. Three patients in the observation group were satisfied with the results after reinjection, and one patient in the control group was satisfied with the results after reinjection, three patients were not satisfied with the results, and four patients were satisfied with the prosthesis augmentation rhinoplasty. In the observation group, there were 37 cases of excellent satisfaction, 5 cases of good satisfaction, and the overall satisfaction was 100%; in the control group, there were 20 cases of excellent satisfaction, 15 cases of good satisfaction, 7 cases of bad satisfaction, and the satisfaction was 83.3%. The former was better than the latter.Conclusions:In view of superiorities such as lower complications with long-lasting effect, high fat survival rate and high satisfaction in local augmentation rhinoplasty, SVF-gel injection is especially suitable for patients who cannot accept autologous bone, prosthesis and allograft tissue filler for augmentation rhinoplasty.
5.A prognostic model of intrahepatic cholangiocarcinoma after curative intent resection based on Bayesian network
Chen CHEN ; Yuhan WU ; Jingwei ZHANG ; Yinghe QIU ; Hong WU ; Qi LI ; Tianqiang SONG ; Yu HE ; Xianhan MAO ; Wenlong ZHAI ; Zhangjun CHENG ; Jingdong LI ; Shubin SI ; Zhiqiang CAI ; Zhimin GENG ; Zhaohui TANG
Chinese Journal of Surgery 2021;59(4):265-271
Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.
6.Progress in the treatment of diabetic foot with mesenchymal stromal cell therapy
Xinyu LIU ; Tingrui ZHAO ; Mogen ZHANG ; Zhaohui ZHAI ; Yuli LI
Chinese Journal of Plastic Surgery 2021;37(12):1404-1409
Diabetes has become a chronic disease endangering people’s health all over the world. This translated into a huge economic burdento society. Diabetic foot ulcer is difficult to heal due to ischemia, infection, neuropathy and other reasons, which leads to increased risk of amputation and infectious death. Amputation is the main method in traditional treatment, which is adverse to improve the quality of patients’ lives. Thus, more and more scientists pay attention to the treatment of diabetic foot with mesenchymal cells. In this article, we will give a general introduction to the multi-functional mesenchymal stromal cells and explain the mechanism of their use in diabetic foot ulcer, as well as introduce several cases of clinical and preclinical studies on the application of mesenchymal cells in the treatment of diabetes ulcers in foreign countries.
7.A prognostic model of intrahepatic cholangiocarcinoma after curative intent resection based on Bayesian network
Chen CHEN ; Yuhan WU ; Jingwei ZHANG ; Yinghe QIU ; Hong WU ; Qi LI ; Tianqiang SONG ; Yu HE ; Xianhan MAO ; Wenlong ZHAI ; Zhangjun CHENG ; Jingdong LI ; Shubin SI ; Zhiqiang CAI ; Zhimin GENG ; Zhaohui TANG
Chinese Journal of Surgery 2021;59(4):265-271
Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.
8.Progress in the treatment of diabetic foot with mesenchymal stromal cell therapy
Xinyu LIU ; Tingrui ZHAO ; Mogen ZHANG ; Zhaohui ZHAI ; Yuli LI
Chinese Journal of Plastic Surgery 2021;37(12):1404-1409
Diabetes has become a chronic disease endangering people’s health all over the world. This translated into a huge economic burdento society. Diabetic foot ulcer is difficult to heal due to ischemia, infection, neuropathy and other reasons, which leads to increased risk of amputation and infectious death. Amputation is the main method in traditional treatment, which is adverse to improve the quality of patients’ lives. Thus, more and more scientists pay attention to the treatment of diabetic foot with mesenchymal cells. In this article, we will give a general introduction to the multi-functional mesenchymal stromal cells and explain the mechanism of their use in diabetic foot ulcer, as well as introduce several cases of clinical and preclinical studies on the application of mesenchymal cells in the treatment of diabetes ulcers in foreign countries.
9.Application value of different lymph node staging system in predicting prognosis of patients with intrahepatic cholangiocarcinoma
Chen CHEN ; Yuhan WU ; Qi LI ; Hong WU ; Yinghe QIU ; Tianqiang SONG ; Xianhai MAO ; Yu HE ; Zhangjun CHENG ; Wenlong ZHAI ; Jingdong LI ; Zhimin GENG ; Zhaohui TANG
Chinese Journal of Surgery 2020;58(4):295-302
Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.
10.Application value of different lymph node staging system in predicting prognosis of patients with intrahepatic cholangiocarcinoma
Chen CHEN ; Yuhan WU ; Qi LI ; Hong WU ; Yinghe QIU ; Tianqiang SONG ; Xianhai MAO ; Yu HE ; Zhangjun CHENG ; Wenlong ZHAI ; Jingdong LI ; Zhimin GENG ; Zhaohui TANG
Chinese Journal of Surgery 2020;58(4):295-302
Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

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